Pneumonia‐induced sepsis in mice: temporal study of inflammatory and cardiovascular parameters

The aim of the present work is to provide a better comprehension of the pneumonia‐induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF‐α and IL‐1β levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS‐2 expression appeared late after bacteria inoculation, whereas levels of NOS‐1 and NOS‐3 were unchanged. The high NOS‐2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae‐induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology.     

Guidelines and considerations for conducting experiments using tissue microarrays

Tissue microarrays (TMAs) represent a powerful method for undertaking large‐scale tissue‐based biomarker studies. While TMAs offer several advantages, there are a number of issues specific to their use which need to be considered when employing this method. Given the investment in TMA‐based research, guidance on design and execution of experiments will be of benefit and should help researchers new to TMA‐based studies to avoid known pitfalls. Furthermore, a consensus on quality standards for TMA‐based experiments should improve the robustness and reproducibility of studies, thereby increasing the likelihood of identifying clinically useful biomarkers. In order to address these issues, the National Cancer Research Institute Biomarker and Imaging Clinical Studies Group organized a 1‐day TMA workshop held in Nottingham in May 2012. The document herein summarizes the conclusions from the workshop. It includes guidance and considerations on all aspects of TMA‐based research, including the pre‐analytical stages of experimental design, the analytical stages of data acquisition, and the postanalytical stages of data analysis. A checklist is presented which can be used both for planning a TMA experiment and interpreting the results of such an experiment. For studies of cancer biomarkers, this checklist could be used as a supplement to the REMARK guidelines.     

Acquired Left Ventricular Submitral Aneurysms in the Course of Takayasu Arteritis in a Child

A 9‐year‐old black African boy was hospitalized for heart failure revealing a severe left ventricular dysfunction associated with dilated cardiomyopathy, two submitral aneurysms, occlusion of the circumflex artery and a giant coronary artery aneurysm on the proximal left anterior descending artery. The boy was coinfected with human immunodeficiency virus and Mycobacterium tuberculosis. Though rare, association of Takayasu arteritis and submitral aneurysm leads to rethinking the pathogenesis of submitral aneurysm and suggests that some of them may be acquired. In our case, a common inflammatory process, possibly triggered by tuberculosis or HIV, may underlie Takayasu and submitral aneurysms.     

Initial HRCT findings of novel influenza A (H1N1) infection

Please cite this paper as: Yuan et al. (2012) Initial HRCT findings of novel influenza A (H1N1) infection. Influenza and Other Respiratory Viruses 6(601), e114–e119. Objectives The aim of our study was to describe the presentation and illustrate the imaging features of chest high‐resolution computed tomography (HRCT) of patients with novel influenza A (H1N1) virus infection. Methods Data were collected from 163 hospitalized patients between November 2009 and March 2011, who fulfilled the clinical criteria for H1N1 influenza infection and underwent HRCT examinations within 24 hours of admission. Results Abnormal findings were observed in 40·5% of the patients. The patients with positive imaging findings were significantly older than patients with normal HRCT findings (P = 0·02). The most common finding was ground‐glass opacity (GGO) (n = 35). Interlobular septal thickening (n = 31) and centrilobular nodules (n = 30) were the second most frequent findings. Other common findings were consolidation, reticulation, and linear shadow. The most common imaging finding for lung involvement was GGO with a patchy pattern. Pulmonary involvement of the disease may be extensive and variable, but the total volume of affected lung was mostly <1 lobe. Conclusion The baseline HRCT may be valuable and suggestive even for non‐severe H1N1 infections. When a severe case or a evolution is suspected, chest CT could be essential both for determining the precise extent of parenchymal damage and for monitoring its evolution.     

Radioiodination and bioevaluation of nitrofurantoin for urinary tract imaging

Nitrofurantoin (NF) was labeled with iodine‐125 via electrophilic substitution reaction. Some factors affecting the radiochemical yield of ¹²⁵I‐NF, such as NF concentration, chloramine‐T (CAT) concentration, pH of the reaction mixture, reaction time, temperature, and reaction medium, were studied. The maximum yield of ¹²⁵I‐NF (90%) was obtained by using 3.7 MBq of Na¹²⁵I, 1 mM CAT, 1 mM NF in DMF, at pH 2 and 60 °C within 5 min. The specific activity of ¹²⁵I‐NF reaches 33.3 MBq/0.2 mmol, and the ¹²⁵I‐NF was completely separated and purified by means of high pressure liquid chromatography. The biological distribution in normal mice indicates the suitability of radioiodinated NF for urinary tract imaging. Copyright © 2012 John Wiley & Sons, Ltd.     

Does JC virus have a role in the etiology and prognosis of Egyptian colorectal carcinoma?

John Cunningham virus (JCV) encodes an oncogenic T‐antigen, which is capable of interacting with key growth regulatory pathways. JCV definite role as causal agent of human cancer, still awaits final confirmation. The present study was conducted to assess the possible role of JCV in Egyptian colorectal carcinoma (CRC) and correlate the expression with the clinicopathological features and survival. JCV in situ hybridization (ISH) signals and large T antigen immunoreactivity were examined in 87 colonic specimens. Positive glandular JCV ISH signals were detected in 20%, 25% and 40% of normal, adenoma and CRC cases respectively. Stromal JCV ISH signals were identified in 26% of CRC cases and 5% of adenoma however, normal mucosa did not show stromal positivity with significant difference (p = 0.03). Glandular JCV expression was significantly associated with high grade (p = 0.03), high mitotic index (p=0.02) and low apoptotic index (p = 0.00). Positive stromal signals were significantly associated with low apoptosis (p = 0.00). No positive nuclear immunostaining of JCV large T antigen was detected in all specimens. JCV stromal expression was the 2nd most powerful indicator of short survival and bad prognosis (p = 0.03) in CRC patients. JCV might play an etiological role in CRC tumorogenesis and short survival in Egyptian CRC patients.